Long-term goal is to develop an objective rapid non-invasive, in vivo means of measuring personal stress history. We propose to demonstrate and validate the use of tooth enamel as an index of childhood stressor exposures, permanently recorded during enamel biomineralization via fossilized incremental growth lines, daily cross-striations as well as longer-range markings, striae of Retzius, broadly analogous to the record of droughts and fires captured in the growth rings of a tree. We have recently shown that an enamel biomarker corresponds to body size and to lamellar bone densitometry, confirming it as a surrogate for other important patterns of body regulation. We hypothesize that: Analysis of enamel in third molar teeth is a biomarker measure of a person's stress history from approximately 8 to 11 years of age. Growing evidence links early life stress exposure and experience, including socio-economic status and harsh/chaotic and/or non-nurturant childhood environments, to adult health trajectories including elevated cardiovascular and other biological risk profiles, impaired immune function, increased risks for multiple chronic conditions, as well as decreased overall longevity, consistent with McEwan's concept of allostatic load describing the cumulative physiologic cost of chronic exposure to the neural, neuroendocrine and neuroendocrine-immune regulatory systems' stress responses over the course of an individual's lifetime. An objective record of childhood stressors, containing both linear and cumulative data, rather than a subjective history, would be of extreme clinical value. It would reduce reliance on subjective, and possibly inaccurate or reluctant, reports on distant events and conditions, and on expensive snapshot lab tests. Such a record would be crucial in identifying vulnerable individuals who may be at increased risk to a wide range of adverse health outcomes; earlier identification of such individuals would offer opportunities for potentially more effective interventions to avert onset of frank disease pathology. Unlike other biomarkers, tooth enamel is inert and cannot be healed, modified, or collect more stress damage after formation, or during adulthood. Teeth capture overlapping enamel records from as early as 4 months in-utero to as late as 11 years after birth. Anthropologists have long used histological enamel records to measure the influence of a variety of external stressors, including diet, emotional stressors, and disease, in modern, historic, and fossil populations. These data have unequivocally established the tooth enamel record of childhood stressors. We will extend this model to: (1) measure long-term and cumulative stress records, as well as linear short-term acute stressors; (2) non-invasive surface and subsurface imaging; (3) contemporary defined populations. We integrate expertise and emergent technology in the necessary behavioral, dental, histological, surface and subsurface imaging, mathematical, and analytical domains so as to demonstrate that early stress, recorded in tooth enamel, is related to stress-related risk factors known to be associated with illicit drug-seeking leading to addiction. We will define a future non-invasive clinical screening instrument. PUBLIC HEALTH RELEVANCE: We propose to demonstrate and validate the use of tooth enamel as an immutable index of childhood stressor exposures, permanently recorded during enamel biomineralization. We seek to relate early stress, recorded in tooth enamel, to adverse childhood environmental stressors, life events, and traumas known to be associated with illicit drug-seeking leading to addiction. Such an objective record would be crucial in identifying vulnerable individuals who may be at increased risk to a wide range of adverse health outcomes; earlier identification of such individuals would offer opportunities for potentially more effective interventions to avert onset of frank disease pathology. We will define a future non-invasive clinical screening instrument.